Mesothelin is shed from cells by the action of membrane bound proteases. We believe shedding is important for the carcinogenic effect of mesothelin. We have previously established that ADAM 17 is important for mesothelin shedding and evaluated the effect of shedding inhibitors. These only have modest activity. We have recently found that ADAM 10 may also be involved in shedding and are investigating its role in several different cancers. We have initiated a collaboration with GaloreTex to identify new mesothelin specific inhibitors which could be useful in cancer treatment.